Streptococcus pneumoniae (pneumococcus) is a major worldwide pathogen of humans, causing serious infections in the lungs, central nervous system, blood, and middle ear. Current vaccines and antibiotics do not provide equal or adequate protection for individuals of all ages, infections at all sites, or against pneumococci of all strains (serotypes). Therefore, it would be valuable to devise a pneumococcal vaccine based on relatively invariant pathogen-encoded proteins that are present in all or most strains and that can elicit protective antibodies. In addition, it would be valuable to be able to augment the abilities of these proteins to elicit protective antibody responses. Aim 1. To determine if the host-encoded immune system molecules, BLyS and C3d, can enhance potentially protective immune responses to the pneumococcal protein PspA. Studies under this aim will also address the mechanisms by which host proteins mediate any enhancements of the immune responses to PspA. Aim 2. To determine if a protein derived from the pneumococcus (PspA) can be more effective than a non-pneumococcal protein, when physically linked to pneumococcal capsular polysaccharides (PS), at enhancing the PS-specific serum antibody response. Aim 3. To determine how, in comparison to normal mice, mice lacking the taci gene (involved in anti-PS antibody responses) respond to pneumococcal PS-protein conjugate vaccines and to pneumococci. This aim will also determine if taci-deficient mice, immunized or unimmunized, have increased susceptibility to pneumococcal infection.